Evidence map›Paper›PMID 42303907›Full record

ArticleMolecular biomedicine2026

SEMA6A inhibits tumor progression and boosts anti-tumor immunity via blocking the ISG15/TGFβ axis in colorectal cancer.

Fang Zhang, Rixin Zhang, Zheng Yan, Jinbao Zong, Mingxuan Zhou, Tiegang Li, Yufang Hou, Silin Lv, Zifan Zeng, Wenyi Zhao and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular biomedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Fang Zhang *State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Rixin Zhang *State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Zheng YanState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Jinbao ZongClinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
Mingxuan ZhouState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Tiegang LiState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Yufang HouState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Silin LvState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Zifan ZengState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Wenyi ZhaoState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Yixin ZhouState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Zengni ZhuState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Siying HuangState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China.
Min YangState Key Laboratory of Digestive Health, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 2 Nanwei Road, Beijing, 100050, China. minyang@imm.ac.cn.ORCID http://orcid.org/0000-0002-3827-5961

Funding

National Natural Science Foundation of China No. 82473958
6 · The paper itself

Abstract

Semaphorins (SEMAs) comprise a diverse family of membrane-associated proteins whose dysregulation is implicated in various cancers, influencing tumor progression and immune responses. However, the role of SEMAs in colorectal cancer (CRC) remains underexplored. This study demonstrates that Semaphorin 6A (SEMA6A) is downregulated in CRC tissues, with low SEMA6A expression correlating with increased tumor aggressiveness and poor prognosis in CRC patients. Functional assays illustrate that SEMA6A overexpression exerts anti-tumor effects both in vitro and in vivo, while integrated RNA-seq and proteomic analyses identify ISG15 as a key downstream effector negatively regulated by SEMA6A. Mechanistically, SEMA6A inhibits the JAK-STAT3 pathway, leading to decreased ISG15 expression, which in turn abrogates the ISGylation-dependent stabilization of TGF-β1 and promotes its degradation, as confirmed by molecular docking, co-immunoprecipitation, and cycloheximide chase assays. Consequently, in vitro co-culture assays and in vivo experiments reveal that SEMA6A overexpression in tumor cells enhances CD8

Indexed as

Colorectal NeoplasmsCytokinesSemaphorinsTransforming Growth Factor betaUbiquitinsAnimalsCD8-Positive T-LymphocytesCell Line, TumorDisease ProgressionFemaleGene Expression Regulation, NeoplasticHumansMaleMiceSignal TransductionCytokinesISG15 protein, humanSEMA6A protein, humanSemaphorinsTransforming Growth Factor betaUbiquitinsColorectal cancerImmunotherapyISG15PrognosisSEMA6A

Identifiers

PMID42303907
PMCPMC13272749

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.